Vial rubber stopper

ABSTRACT

Provided is a vial rubber stopper using multiple types of rubber to prevent the vial rubber stopper from being scraped and from sticking to a presser plate. The vial rubber stopper includes: a cap portion having a flange; a piercing area formed to have a recess at a top surface of the cap portion and configured to traverse longitudinally the cap portion in an axial direction from the recess to a bottom surface of the cap portion; and a leg portion formed on the bottom surface of said cap portion in a way of extending downward and located outside the piercing area with respect to an axial center of said cap portion. The piercing area is formed of rubber having rubber hardness from 20 to 35, and the top surface other than the recess of the cap portion is formed of rubber having rubber hardness from 58 to 90.

TECHNICAL FIELD

The present invention relates to a vial rubber stopper, and moreparticularly to a vial rubber stopper suitable for production and/or useof a freeze-dried medical agent.

BACKGROUND ART

A vial or an ampule is used as a container for storing a little amountof drug solution. The vial, mainly a small container made of glass,plastics or the like, is sealed with an opening portion of the containerbeing capped by a rubber stopper. Since it is possible to have a devicesuch as a syringe or the like communicated with the container byinserting a hollow needle through the rubber stopper without breaking(or destroying) the sealing of the container, the operation can beperformed hygienically without opening the container imprudently.Therefore, such vial is used as a container for various types of medicalagents no matter it is a liquid medical agent or a powder medical agent.

Generally, a vial is produced according to the following procedure. Apredefined amount of medical agent is filled into a cylindricalcontainer having an upper portion thereof opened, and a leg portion ofthe rubber stopper is softly inserted into the opening (half capped). Aplurality of such prepared vials are capped in a capper. (In the case ofa vial containing a freeze-dried drug product, the vial is put into afreeze dryer at the half capped state to freeze-dry the drug product,and thereafter the vial is capped in a capper.) The capping is performedby lowering a presser plate from the upper side to press the rubberstopper into the vial.

Vials are used and produced as mentioned above; however, userequirements are contradictory to production requirements. In the use,the rubber stopper is pierced through by a hollow needle. If rubberhardness is high, at the time when the hollow needle pierces the rubberstopper, the rubber stopper will be scrapped, resulting in the so-calledcoring, and it is possible that minute pieces of rubber (impurities)will fall into the vial. Therefore, from the viewpoint of preventing thecoring, it is desired to decrease the hardness of the portion to bepierced by the hollow needle.

On the contrary, in the production, the presser plate and the rubberstopper are pressed to contact each other in a capping step. If a topsurface of the rubber stopper sticks to the presser plate, at the timewhen the presser is elevated, the vial will be elevated together withthe rubber stopper; as the elevated vial falls down, it may break, whichmay make the whole lot unusable. Therefore, from the viewpoint ofpreventing the presser plate and the rubber stopper from sticking toeach other, it is desired to increase the hardness of the top surface ofthe rubber stopper.

In order to offer multiple functions to a rubber stopper, the rubberstopper is formed of multiple rubber materials, such as the onedisclosed in Japanese Patent Laying-Open No. 2004-231216. From theviewpoint of keeping medical agents stable for a long term in a vial andpreventing the rubber stopper from being degenerated by the medicalagents, the vial is entirely formed of chlorinated polyethylene rubber,chlorosulfonated polyethylene rubber or the like; and in order tocompensate for resealing capability of a pierced hole which is notpossessed by the multiple rubber materials, the portion to be pierced bythe needle is formed of natural rubber, isoprene rubber or butadienerubber.

CITATION LIST Patent Document

-   PTD 1: Japanese Patent Laying-Open No. 2004-231216

SUMMARY OF INVENTION Technical Problem

However, taken into consideration the prevention of the coring and thesticking to the presser plate, the configuration of the rubber stopperof PTD1 is insufficient. The rubber stopper of PTD1 prevents thesticking to the presser plate through the way of providing a projectionon the top surface of a cap portion; however, in actual use, it isimpossible to prevent the sticking to the presser plate merely byproviding a projection on the top surface, thereby, the vial is still inthe risk of breaking. Moreover, it is suggested that the portion to bepierced by the needle is formed of natural rubber, isoprene rubber,butadiene rubber or the like on the consideration of the resealingcapability; however, since these rubber materials have great gaspermeability, the connection of the interior portion of the vial and theexterior air through the intermediary of these rubber materials maycarry an adverse influence on the state of medical agents stored in thevial. As a solution to the coring, a high elastic rubber must bedisposed to traverse longitudinally from the top surface to a bottomsurface of the cap portion; thereby, it is not desired to use theserubber materials. Therefore, under the precondition of maintaining thestorage stability of medical agents (degeneration of medical agents,deterioration of the rubber stopper and the like) in the vial, it isdesired to produce a vial rubber stopper in combination with such kindof rubber capable of preventing the sticking to the presser plate andthe occurrence of the coring.

An object of the present invention is to provide a vial rubber stopperfree from sticking to the presser plate and the occurrence of the coringby using multiple types of rubber.

After keen examinations, the inventors of the present invention figuredout the following invention. A vial rubber stopper includes a capportion having a flange, a piercing area formed to have a recess at atop surface of the cap portion and configured to traverse longitudinallythe cap portion from the recess to a bottom surface of the cap portion,and a leg portion formed on the bottom surface of the cap portion in away of extending downward and located outside the piercing area withrespect to an axial center of said cap portion. The piercing area isformed of rubber having rubber hardness from 20 to 35, and the topsurface other than the recess of the cap portion is formed of rubberhaving rubber hardness from 58 to 90.

Further, it is acceptable that the vial rubber stopper, excluding thetop surface other than the recess of the cap portion, is formed ofrubber having rubber hardness from 20 to 35, and it is also acceptablethat the vial rubber stopper, excluding the top surface other than therecess and a side portion of the cap portion, is formed of rubber havingrubber hardness from 20 to 35. Furthermore, it is acceptable that thevial rubber stopper, excluding the top surface other than the recess andthe flange of said cap portion, is formed of rubber having rubberhardness from 20 to 35.

According to the vial rubber stopper mentioned above, since the topsurface of the cap portion being pressed by the presser plate is formedof rubber having high rubber hardness and the portion to be pierced bythe hollow needle is formed of rubber having low rubber hardness, thesticking to the presser plate can be prevented and the occurrence of thecoring can be avoided. Thereby, the present invention has been achievedfor the purpose of preventing the vial from breaking in the productionand preventing the minute rubber pieces from being mixed into medicalagents in the use.

Advantageous Effects of Invention

The vial rubber stopper of the present invention is free from stickingto the presser plate and the occurrence of the coring, and thus it ispreferably applicable to medical services.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates a vial rubber stopper according to an embodiment ofthe present invention, in which (a) is a view of a top surface and (b)is a longitudinal sectional view;

FIG. 2 illustrates a vial rubber stopper according to another embodimentof the present invention, in which (a) is a view of a top surface and(b) is a longitudinal sectional view;

FIG. 3 is a longitudinal sectional view of a vial rubber stopperaccording to another embodiment of the present invention;

FIG. 4 is a longitudinal sectional view of a vial rubber stopperaccording to another embodiment of the present invention; and

FIG. 5 is a longitudinal sectional view of a vial rubber stopperaccording to another embodiment of the present invention.

DESCRIPTION OF EMBODIMENTS

Hereinafter, a vial rubber stopper of the present invention will bedescribed with reference to the drawings. It should be noted that thepresent invention is not limited to embodiments illustrated in thedrawings.

FIG. 1 is a longitudinal sectional view of a vial rubber stopperaccording to an embodiment of the present invention. FIG. 2 is alongitudinal sectional view of a vial rubber stopper having multiplepiercing areas according to an embodiment of the present invention. FIG.3 is a longitudinal sectional view of a vial rubber stopper according toanother embodiment of the present invention. FIG. 4 is a longitudinalsectional view of a vial rubber stopper according to another embodimentof the present invention. FIG. 5 is a longitudinal sectional view of avial rubber stopper according to another embodiment of the presentinvention.

The vial rubber stopper of the present invention will be described withFIG. 1 as an example. A cap portion 1 having a flange includes a recess2 at the center of a top surface, and multiple projections are formedradiating from the recess in a predetermined direction at equalintervals. A piercing area is disposed at the center of the cap portion,traversing longitudinally from the recess to a bottom surface. Twocylindrical leg portions extending downward are formed on the bottomsurface of the cap portion to surround the piercing area. An inclinationportion 11 inclining toward an out-pouring opening is formed at thefront of an upper portion of a container body 1. The piercing area isformed of chlorinated butyl rubber containing no clay (rubber having lowrubber hardness), and the other portion excluding the piercing area isformed of rubber having high rubber hardness which is obtained bycombining 60 parts of clay with 100 parts of chlorinated butyl rubber.By selecting the rubber as mentioned above, the coring will not occureven though a hollow needle pierces therethrough, and the sticking to apresser plate will not happen.

In the above embodiment, chlorinated butyl rubber is used for both therubber having high rubber hardness and the rubber having low rubberhardness. Since chlorinated butyl rubber has low gas permeability and isfree from being deteriorated by medical agents and being eluted by themedical agents, it can be used preferably. The rubber hardness of therubber stopper is adjusted by formulating clay in chlorinated butylrubber. Chlorinated butyl rubber is given as an example but not limitedthereto, and any rubber may be used if the rubber is rich inairtightness which can be used as the rubber stopper of a vial, andpossesses no such bad influences as being deteriorated by the medicalagents inside the vial and/or being eluted by the medical agents insidethe vial. In addition, the rubber for the top surface of the cap portionof the rubber stopper is not particularly limited if the rubber has therubber hardness preventing the sticking of the top surface to thepresser plate, and the rubber for the piercing area is also notparticularly limited if the rubber has the rubber hardness avoiding theoccurrence of the coring caused by the piercing of a hollow needle. Inthe above embodiment, both the top surface of the cap portion and thepiercing area are formed of chlorinated butyl rubber; it is acceptablethat the top surface of the cap portion and the piercing area are formedof different types of rubber.

For the piercing area in the above embodiment, one recess is formed atthe center of the top surface of the cap portion, and the piercing areais formed to traverse longitudinally from the recess to the bottomsurface of the cap portion. However, the recess may not be disposed atthe center of the top surface of the cap portion, and the recess is notlimited to one but in plural numbers. For example as illustrated in FIG.2, it is acceptable that two recesses are provided at a predeterminedinterval from the center of the top surface of the cap portion and thepiercing area is disposed to traverse longitudinally from each recess tothe bottom surface of the cap portion. In this case, the piercing areais located inside the area surrounded by the leg portion of the capportion. The configuration of the piercing area having a recess lowerthan the top surface of the cap portion makes it possible to prevent thepiercing area from contacting the presser plate and avoid the stickingof the piercing area to the presser plate.

For the leg portion, the shape of the leg portion is not particularlylimited if it can keep the vial airtight and/or liquid-tight after it isinserted into an opening of the vial. The leg portion may simply have acylindrical shape. Preferably, in order to be used as a rubber stopperfor a freeze-dried vial, it is acceptable that a portion of thecylindrical body is cut away, and it is also acceptable that a hole isdisposed in the type described in the above embodiment, a C-shapedcylindrical body, or a cylinder close to the side of the cap portion.

As another embodiment, it is acceptable that the top surface of the capportion other than the recess and the flange thereof are formed ofrubber having the high rubber hardness and the other portion is formedof rubber having the low rubber hardness, as illustrated in FIG. 3; itis also acceptable that the top surface of the cap portion other thanthe recess and a side portion thereof are formed of rubber having thehigh rubber hardness and the other portion is formed of rubber havingthe low rubber hardness, as illustrated in FIG. 4; it is furtheracceptable that the portion of the top surface of the cap portion otherthan the recess and the flange, which has no contact with the vial, isformed of rubber having the high rubber hardness and the other portionis formed of rubber having the low rubber hardness, as illustrated inFIG. 5. Particularly, if the rubber stopper is formed as illustrated inFIG. 4 or FIG. 5, only the rubber having the low rubber hardnesscontacts the vial, which makes it easier to keep the airtightness.

Hereinafter, a production method will be described with the vial rubberstopper in FIG. 1 as an example. Firstly, rubber material having thehigh rubber hardness is introduced into a first die having a circulardoughnut shape, the die is closed and the rubber is semi-vulcanized tooffer a primary molding article. Thereafter, the primary molding articleis transferred into a second die, rubber material having the low rubberhardness is introduced, the die is closed and the rubber is fullyvulcanized to offer the vial rubber stopper. The formulation example offilling agents is listed in Table 1.

TABLE 1 high hardness rubber low hardness rubber chlorinated butylrubber 100 100 talc 30 30 clay 60 0 hydrated silica powder 15 5 titaniumoxide 2 2 carbon black master-batch 0.12 0.12 zinc oxide 5 5sulfur-containing compound 1.5 1.5

With respect to the rubber stoppers obtained according to theformulations in Table 1, after a rubber stopper was capped into a vial,a boundary separation test was performed on 10 samples by pressing thepiercing area with a metal rod of φ6 mm from the top surface of therubber stopper with a force of 60 N to confirm whether or not thepiercing area separates from the other portion, and the boundaryseparation was found in none of the 10 samples.

The production method is not limited to the above, and the rubberstopper may be produced according to various production methods. Forexample, once after the rubber having the high rubber hardness isobtained through semi-vulcanization, the portion corresponding to thepiercing area is hollowed out and the hollowed portion is filled withthe rubber material having the low rubber hardness; thereafter, the dieis closed and the rubber is fully vulcanized to offer the vial rubberstopper.

With respect to the rubber stopper obtained according to Table 1, inorder to confirm whether or not the sticking to the presser plate in thecapping operation and the coring in the piercing operation will occur, atop surface-plate sticking test and a coring test were performed. Theresult is that neither the rubber stopper stuck to the plate nor thecoring occurred.

<Top Surface-Plate Sticking Test>

The rubber stopper was half capped into each of 25 vials with SUS#400plate, and after being kept under a pressing pressure of 5.0 Kgf/cm² for15 minutes, the SUS plate was elevated. At this moment, the intervalfrom a time when the stuck vial was elevated to a time when the vialfell and the number of tilted vials were counted.

With respect to the rubber stoppers obtained according to Table 1, nonestuck to the plate. Since none stuck to the plate, the number of tiltedvials was zero.

<Coring Test>

For 10 rubber stoppers, a hollow needle (18G11/2′ RB metal needleproduced by Nipro) was pierced through the piercing area of each rubberstopper at a speed of 3000 mm/min for 50 times, whether or not rubberpieces and rubber notches are present was confirmed.

With respect to the vial rubber stoppers obtained according to Table 1,the rubber hardness was measured by using a micro rubber hardness gaugeMD-1 capa (by KOBUNSHI KEIKI CO., LTD.). The rubber hardness of thepiercing area was 30 and the rubber hardness of the portions other thanthe piercing area was 65. In addition to the above formulations, thevial rubber stopper was made by using various types of rubber. Theformulation example of filling agents is listed in Table 2. The vialrubber stopper was made by using the types of rubber listed in Table 2as a rubber having the high rubber hardness and a rubber having the lowrubber hardness, respectively.

TABLE 2 formulation A formulation B formulation C formulation Dformulation E formulation F formulation G chlorinated 100 100 100 100100 100 100 butyl rubber talc 25 25 50 60 65 25 30 silica 5 10 — — — 25— UHMWPE — — 5 10 15 10 60 titanium 1 1 2 1 1 1 1 oxide carbon black0.12 0.12 0.12 0.12 0.12 0.12 0.12 master-batch hydrotalcite 7 7 7 7 7 77 sulfur- 0.7 0.8 1 1 1 1 1 containing urea vulcanizing agent UHMWPE =Ultra high molecular weight polyethylene

With respect to the rubber stoppers in the above, the top surface-platesticking test and the coring test were performed similarly. The rubberhardness of formulations A to G and the results of the tests were listedin Table 3. The rubber hardness exhibiting the effect of preventing thesticking to the presser plate is from 58 to 90, and the rubber hardnesswithout occurrence of the coring is from 20 to 35. Thereby, the rubberhardness from 20 to 90 holds the value capable of exhibiting the rubberfunctions.

TABLE 3 formulation A formulation B formulation C formulation Dformulation E formulation F formulation G rubber 30 35 40 43 47 50 58hardness number of 15 9 2 1 3 9 0 tilted vials coring 0 0 2 19 33 34 50occurrence number

INDUSTRIAL APPLICABILITY

As mentioned above, since the vial rubber stopper of the presentinvention is free from sticking to the presser plate and the occurrenceof the coring, it is preferably applicable to medical services.

REFERENCE SIGNS LIST

1: rubber stopper; 2: piercing area; 3: cap portion; 4: leg portion

1. A vial rubber stopper comprising: a cap portion having a flange; apiercing area formed to have a recess at a top surface of the capportion and configured to traverse longitudinally said cap portion fromsaid recess to a bottom surface of the cap portion in an axialdirection; and a leg portion formed on the bottom surface of said capportion in a way of extending downward and located outside the piercingarea with respect to an axial center of said cap portion, said piercingarea being formed of rubber having rubber hardness from 20 to 35, andthe top surface other than said recess of said cap portion being formedof rubber having rubber hardness from 58 to
 90. 2. The vial rubberstopper according to claim 1, wherein the vial rubber stopper, excludingthe top surface other than said recess of said cap portion, is formed ofrubber having rubber hardness from 20 to
 35. 3. The vial rubber stopperaccording to claim 1, wherein the vial rubber stopper, excluding the topsurface other than said recess and a side portion of said cap portion,is formed of rubber having rubber hardness from 20 to
 35. 4. The vialrubber stopper according to claim 1, wherein the vial rubber stopper,excluding the top surface other than said recess and said flange of saidcap portion, is formed of rubber having rubber hardness from 20 to 35.